High incidence of high-risk HPV in benign and malignant lesions of the larynx

Abstract

Abstract. The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffinembedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5 + /GP6 + consensus PCR and E6/E7 type-specific PCR for HPV types 6,11,16,18,31,33,35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10 -6 ). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV + tumor group (100% p16 + , 56% p53 + and 97% EGFR + ) and in the HPV -or low-risk (lr) HPV + tumor group (92% p16 + , 66% p53 + and 100% EGFR + ). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV + subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV -subgroup.

Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma

“…High-risk-HPV DNA has been found in benign and normal tissue of the larynx (Garcia-Milian et al , 1998; Duray et al , 2011), supporting the idea that HPV DNA presence alone cannot demonstrate causality. The concept for causal involvement of mucosal HPV in the pathogenesis of SCC includes: (a) presence of at least one viral genome copy per tumour cell, (b) active transcription of the viral oncogenes E6 and E7 and (c) interaction of the viral oncoproteins with central cellular regulator proteins of cell cycle and apoptosis signalling (Dyson et al , 1989; Scheffner et al , 1990; zur Hausen, 2006).…”

Epidemiologic Trends in Head and Neck Cancer and Aids in Diagnosis

“…Numerous methodologies exist for direct testing for HPV, however, in situ hybridization is the most universally used method allowing for screening of all known high risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66) in one test on standard paraffin tissue sections 66, 67 . Limited availability of this methodology for testing in the community, and concern for lower sensitivity compared to polymerase chain reaction (PCR) led to the evaluation of p16 as a surrogate marker for the presence of HPV in tumor cells.…”

Proteomic Study of HPV-Positive Head and Neck Cancers: Preliminary Results

“…HPV detection and typing of paraffin-embedded tissues were performed as described in our previous work [9]. DNA extraction was performed using a QIAamp DNA Mini Kit (Qiagen, Benelux, Belgium), according to the manufacturer's protocol.…”

“…Recently, we demonstrated that HPV+ oral SCC patients with a history of tobacco use and/or alcohol consumption have a significantly poorer prognosis compared to HPV− patients [4], and two Swedish studies reported that oral HPV infection is associated with a dramatically increased risk of recurrence in oral SCCs [5, 6]. However, other studies have failed to demonstrate an association between HPV status and prognosis [7–9]. Therefore, it seems clear that the biology of oropharyngeal tumors in younger patients, nondrinkers, and nonsmokers is distinct from that of nonoropharyngeal SCC in older patients and those with a history of tobacco use and/or alcohol consumption [10].…”